{"title":"研究 ADGRE2 的非同义变体 D67N 在慢性髓性白血病中的作用。","authors":"Ayesha Afzal, Harooma Jamshaid, Yasmin Badshah, Maria Shabbir, Janeen H Trembley, Sameen Zafar, Ghulam Murtaza Kamal, Tayyaba Afsar, Fohad Mabood Husain, Suhail Razak","doi":"10.1186/s12885-024-13108-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chronic myeloid leukaemia (CML) is a type of blood cancer that begins in the hematopoietic stem cells. It is primarily characterized by a specific chromosomal aberration, the Philadelphia chromosome. While the fusion gene is a major contributor to CML, several other genes including ADGRE2, that are reported as highly expressed in hematopoietic stem cells and could be utilized as a therapeutic marker in leukemic patients are implicated in the disease's progression. Until recently, little research had been conducted to identify single nucleotide polymorphisms (SNPs) associated with CML. Therefore, this study aims to investigate the influence of non-synonymous variants on the structure and function of the gene encoding adhesion G protein-coupled receptor E2, ADGRE2, and to evaluate their association with CML and its clinical and pathological characteristics.</p><p><strong>Methods: </strong>Non-synonymous SNPs of ADGRE2 were retrieved from the ENSEMBL, COSMIC, and gnomAD genome browsers, and the pathogenicity of deleterious variants was assessed using several established computational tools, including SIFT, CADD, REVEL, PolyPhen, and MetaLR.</p><p><strong>Results: </strong>Various in silico analyses explored the impact of damaging SNP on the function, stability, and structure of EGF-like modules containing mucin-like hormone receptor-like2 (EMR2) protein encoded by the ADGRE2 gene. Genotype analysis was performed on collected blood samples, revealing that altered genotype TT of variant rs765071211 (C/T) was associated significantly with CML patients compared to the control. Further in vitro and in vivo analyses suggest that this SNP holds potential for clinical translation.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536965/pdf/","citationCount":"0","resultStr":"{\"title\":\"Investigating the role of non-synonymous variant D67N of ADGRE2 in chronic myeloid leukemia.\",\"authors\":\"Ayesha Afzal, Harooma Jamshaid, Yasmin Badshah, Maria Shabbir, Janeen H Trembley, Sameen Zafar, Ghulam Murtaza Kamal, Tayyaba Afsar, Fohad Mabood Husain, Suhail Razak\",\"doi\":\"10.1186/s12885-024-13108-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chronic myeloid leukaemia (CML) is a type of blood cancer that begins in the hematopoietic stem cells. It is primarily characterized by a specific chromosomal aberration, the Philadelphia chromosome. While the fusion gene is a major contributor to CML, several other genes including ADGRE2, that are reported as highly expressed in hematopoietic stem cells and could be utilized as a therapeutic marker in leukemic patients are implicated in the disease's progression. Until recently, little research had been conducted to identify single nucleotide polymorphisms (SNPs) associated with CML. Therefore, this study aims to investigate the influence of non-synonymous variants on the structure and function of the gene encoding adhesion G protein-coupled receptor E2, ADGRE2, and to evaluate their association with CML and its clinical and pathological characteristics.</p><p><strong>Methods: </strong>Non-synonymous SNPs of ADGRE2 were retrieved from the ENSEMBL, COSMIC, and gnomAD genome browsers, and the pathogenicity of deleterious variants was assessed using several established computational tools, including SIFT, CADD, REVEL, PolyPhen, and MetaLR.</p><p><strong>Results: </strong>Various in silico analyses explored the impact of damaging SNP on the function, stability, and structure of EGF-like modules containing mucin-like hormone receptor-like2 (EMR2) protein encoded by the ADGRE2 gene. Genotype analysis was performed on collected blood samples, revealing that altered genotype TT of variant rs765071211 (C/T) was associated significantly with CML patients compared to the control. Further in vitro and in vivo analyses suggest that this SNP holds potential for clinical translation.</p>\",\"PeriodicalId\":9131,\"journal\":{\"name\":\"BMC Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-11-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536965/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12885-024-13108-6\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12885-024-13108-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:慢性髓性白血病(CML)是一种始于造血干细胞的血癌。它的主要特征是特定的染色体畸变,即费城染色体。虽然融合基因是导致慢性骨髓性白血病的主要因素,但包括 ADGRE2 在内的其他几个基因在造血干细胞中也有高表达,可用作白血病患者的治疗标记。直到最近,与 CML 相关的单核苷酸多态性(SNPs)研究还很少。因此,本研究旨在探讨非同义变异对编码粘附 G 蛋白偶联受体 E2(ADGRE2)基因的结构和功能的影响,并评估它们与 CML 及其临床和病理特征的关联:从ENSEMBL、COSMIC和gnomAD基因组浏览器中检索了ADGRE2的非同义SNPs,并使用SIFT、CADD、REVEL、PolyPhen和MetaLR等几种成熟的计算工具评估了有害变异的致病性:各种硅学分析探讨了损伤性SNP对ADGRE2基因编码的含有粘蛋白样激素受体样2(EMR2)蛋白的EGF样模块的功能、稳定性和结构的影响。对采集的血样进行基因型分析后发现,与对照组相比,变异体 rs765071211 (C/T) 基因型 TT 的改变与慢性骨髓性白血病患者有显著相关性。进一步的体外和体内分析表明,该 SNP 具有临床转化的潜力。
Investigating the role of non-synonymous variant D67N of ADGRE2 in chronic myeloid leukemia.
Background: Chronic myeloid leukaemia (CML) is a type of blood cancer that begins in the hematopoietic stem cells. It is primarily characterized by a specific chromosomal aberration, the Philadelphia chromosome. While the fusion gene is a major contributor to CML, several other genes including ADGRE2, that are reported as highly expressed in hematopoietic stem cells and could be utilized as a therapeutic marker in leukemic patients are implicated in the disease's progression. Until recently, little research had been conducted to identify single nucleotide polymorphisms (SNPs) associated with CML. Therefore, this study aims to investigate the influence of non-synonymous variants on the structure and function of the gene encoding adhesion G protein-coupled receptor E2, ADGRE2, and to evaluate their association with CML and its clinical and pathological characteristics.
Methods: Non-synonymous SNPs of ADGRE2 were retrieved from the ENSEMBL, COSMIC, and gnomAD genome browsers, and the pathogenicity of deleterious variants was assessed using several established computational tools, including SIFT, CADD, REVEL, PolyPhen, and MetaLR.
Results: Various in silico analyses explored the impact of damaging SNP on the function, stability, and structure of EGF-like modules containing mucin-like hormone receptor-like2 (EMR2) protein encoded by the ADGRE2 gene. Genotype analysis was performed on collected blood samples, revealing that altered genotype TT of variant rs765071211 (C/T) was associated significantly with CML patients compared to the control. Further in vitro and in vivo analyses suggest that this SNP holds potential for clinical translation.
期刊介绍:
BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.